It is proposed to investigate the effect of a variety of physiological states on the activity, synthesis and decay of HMG-CoA reductase in liver and intestinal mucosa. This enzyme plays a major role in controlling the rate of synthesis of cholesterol in almost all systems studied. An antiserum to the enzyme present in rat liver has been raised in a goat which is mono-specific for the HMG-CoA reductase protein. The effect of fasting, refeeding, Triton WR-1339 incorporation, hormones (e.g., insulin, thyroxine and corticosteroids) will be investigated. The subunit interactions of the enzyme protein and its effect on overall activity will also be studied. The inhibition of enzyme activity which is observed within 4 hours of feeding cholesterol will also be examined. The effect of cyclic AMP, an apparent inhibitor of enzyme activity, is being evaluated to determine whether or not phosphorylation and dephosphorylation of the enzyme protein is a factor in the inhibition.